Antibiotic or silver versus standard ventriculoperitoneal shunts (BASICS): a multicentre, single-blinded, randomised trial and economic evaluation.

BACKGROUND: Insertion of a ventriculoperitoneal shunt for hydrocephalus is one of the commonest neurosurgical procedures worldwide. Infection of the implanted shunt affects up to 15% of these patients, resulting in prolonged hospital treatment, multiple surgeries, and reduced cognition and quality of life. Our aim was to determine the clinical and cost-effectiveness of antibiotic (rifampicin and clindamycin) or silver shunts compared with standard shunts at reducing infection. METHODS: In this parallel, multicentre, single-blind, randomised controlled trial, we included patients with hydrocephalus of any aetiology undergoing insertion of their first ventriculoperitoneal shunt irrespective of age at 21 regional adult and paediatric neurosurgery centres in the UK and Ireland. Patients were randomly assigned (1:1:1 in random permuted blocks of three or six) to receive standard shunts (standard shunt group), antibiotic-impregnated (0·15% clindamycin and 0·054% rifampicin; antibiotic shunt group), or silver-impregnated shunts (silver shunt group) through a randomisation sequence generated by an independent statistician. All patients and investigators who recorded and analysed the data were masked for group assignment, which was only disclosed to the neurosurgical staff at the time of operation. Participants receiving a shunt without evidence of infection at the time of insertion were followed up for at least 6 months and a maximum of 2 years. The primary outcome was time to shunt failure due the infection and was analysed with Fine and Gray survival regression models for competing risk by intention to treat. This trial is registered with ISRCTN 49474281. FINDINGS: Between June 26, 2013, and Oct 9, 2017, we assessed 3505 patients, of whom 1605 aged up to 91 years were randomly assigned to receive either a standard shunt (n=536), an antibiotic-impregnated shunt (n=538), or a silver shunt (n=531). 1594 had a shunt inserted without evidence of infection at the time of insertion (533 in the standard shunt group, 535 in the antibiotic shunt group, and 526 in the silver shunt group) and were followed up for a median of 22 months (IQR 10-24; 53 withdrew from follow-up). 32 (6%) of 533 evaluable patients in the standard shunt group had a shunt revision for infection, compared with 12 (2%) of 535 evaluable patients in the antibiotic shunt group (cause-specific hazard ratio [csHR] 0·38, 97·5% CI 0·18-0·80, p=0·0038) and 31 (6%) of 526 patients in the silver shunt group (0·99, 0·56-1·74, p=0·96). 135 (25%) patients in the standard shunt group, 127 (23%) in the antibiotic shunt group, and 134 (36%) in the silver shunt group had adverse events, which were not life-threatening and were mostly related to valve or catheter function. INTERPRETATION: The BASICS trial provides evidence to support the adoption of antibiotic shunts in UK patients who are having their first ventriculoperitoneal shunt insertion. This practice will benefit patients of all ages by reducing the risk and harm of shunt infection. FUNDING: UK National Institute for Health Research Health Technology Assessment programme.

Use of Whole-Genome Sequencing of Adenovirus in Immunocompromised Pediatric Patients to Identify Nosocomial Transmission and Mixed-Genotype Infection.

Background: Adenoviruses are significant pathogens for the immunocompromised, arising from primary infection or reinfection. Serotyping is insufficient to support nosocomial transmission investigations. We investigate whether whole-genome sequencing (WGS) provides clinically relevant information on transmission among patients in a pediatric tertiary hospital. Methods: We developed a target-enriched adenovirus WGS technique for clinical samples and retrospectively sequenced 107 adenovirus-positive residual diagnostic samples, including viremias (>5 × 104 copies/mL), from 37 patients collected January 2011-March 2016. Whole-genome sequencing was used to determine genotype and for phylogenetic analysis. Results: Adenovirus sequences were recovered from 105 of 107 samples. Full genome sequences were recovered from all 20 nonspecies C samples and from 36 of 85 species C viruses, with partial genome sequences recovered from the rest. Whole-genome phylogenetic analysis suggested linkage of 3 genotype A31 cases and uncovered an unsuspected epidemiological link to an A31 infection first detected on the same ward 4 years earlier. In 9 samples from 1 patient who died, we identified a mixed genotype adenovirus infection. Conclusions: Adenovirus WGS from clinical samples is possible and useful for genotyping and molecular epidemiology. Whole-genome sequencing identified likely nosocomial transmission with greater resolution than conventional genotyping and distinguished between adenovirus disease due to single or multiple genotypes.

Molecular techniques for diagnosing prosthetic joint infections.

Prosthetic joint infections (PJI) can be broadly classed into two groups: those where there is a strong clinical suspicion of infection and those with clinical uncertainty, including 'aseptic loosening'. Confirmation of infection and identification of the causative organism along with provision of antibiotic susceptibility data are important stages in the management of PJI. Conventional microbiological culture and susceptibility testing is usually sufficient to provide this. However, it may fail due to prior antimicrobial treatment or the presence of unusual and fastidious organisms. Molecular techniques, in particular specific real-time and broad-range PCR, are available for diagnostic use in suspected PJI. In this review, we describe the techniques available, their current strengths, limitations and future development. Real-time pathogen-specific and broad-range PCR (with single sequence determination) are suitable for use as part of the routine diagnostic algorithm for clinically suspected PJI. Further development of broad-range PCR with high-throughput (next-generation) sequencing is necessary to understand the microbiome of the prosthetic joint further before this technique can be used for routine diagnostics in clinically unsuspected PJI, including aseptic loosening.

Long subcutaneous tunnelling reduces infection rates in paediatric external ventricular drains.

PURPOSE: The aim of this study is to report the efficacy of long subcutaneous tunnelling of external ventricular drains in reducing rates of infection and catheter displacement in a paediatric population. METHODS: In children requiring external ventricular drainage, a long-tunnelled drain was placed and managed according to a locally agreed guideline. End points were novel CSF infection incurred during the time of drainage and re-operation to re-site displaced catheters. Data were compared to other published series. RESULTS: One hundred eighty-one long-tunnelled external ventricular drains (LTEVDs) were inserted. The mean age was 6.6 years (range 0-15.5 years). Reasons for insertion included intraventricular haemorrhage (47 %), infection (27 %), tumour-related hydrocephalus (7.2 %), as a temporising measure (17 %) and trauma (2.2 %). The overall new infection rate for LTEVD was 2.76 %. If the 48 cases where LTEVDs were inserted to treat an existing infection are excluded, the infection rate was 3.8 % (5/133). The mean duration of insertion was 10 days (range 0-42 days). Four LTEVDs (2.2 %) were inadvertently dislodged, requiring reinsertion. Thirteen patients required removal of EVD alone. There was a significant difference (p < 0.05) when comparing our infection rate to 14 publications of infection rates in short-tunnelled EVDs; however, there was no difference when comparing our data to three publications using LTEVDs. CONCLUSION: The use of an antibiotic-impregnated LTEVD, managed according to a predefined guideline, is associated with significantly reduced infection and displacement rates when compared with contemporary series. It is suggested that this reduction is of both clinical and economic benefits.

Clostridioides difficile detection and infection in children: are they just small adults?

Clostridioides difficile is a well-recognized healthcare-associated pathogen, with its significance widely recognized in adult populations. Despite this, there is limited data on the significance of detection within paediatric populations, both for individual patient management and wider transmission risk-based considerations. High rates of colonization are understood to occur in infants, with increasing levels up to 11 months, and colonization rates similar to adults by 8 years old. Sources of C. difficile are ubiquitous, with detection in companion animals and food sources, as well as within the clinical and wider environment. Due to the close interactions that occur between children and the environment, it is understandable that increasing recognition is afforded to the community acquisition of C. difficile in children. Other risk factors for the detection of C. difficile in children are similar to those observed in adults, including prior hospitalization and underlying conditions affecting gut health and motility. Recent studies have shown rising awareness of the role of asymptomatic carriage of C. difficile in healthcare transmission. Prior to this, paediatric patient populations were less likely to be screened due to uncertainty regarding the significance of detection; however, this increased awareness has led to a review of possible carriage testing pathways. Despite this increased attention, C. difficile infection remains poorly defined in paediatric populations, with limited dedicated paediatric data sets making comparison challenging. This is further complicated by the fact that infection in children frequently self resolves without additional therapies. Due to this, C. difficile remains a management challenge in paediatric settings.

Next-generation whole genome sequencing identifies the direction of norovirus transmission in linked patients.

BACKGROUND: Noroviruses are a highly transmissible and major cause of nosocomial gastroenteritis resulting in bed and hospital-ward closures. Where hospital outbreaks are suspected, it is important to determine the routes of spread so that appropriate infection-control procedures can be implemented. To investigate a cluster of norovirus cases occurring in children undergoing bone marrow transplant, we undertook norovirus genome sequencing by next-generation methods. Detailed comparison of sequence data from 2 linked cases enabled us to identify the likely direction of spread. METHODS: Norovirus complementary DNA was amplified by overlapping polymerase chain reaction (PCR) from 13 stool samples from 5 diagnostic real-time PCR-positive patients. The amplicons were sequenced by Roche 454, the genomes assembled by de novo assembly, and the data analyzed phylogenetically. RESULTS: Phylogenetic analysis indicated that patients were infected by viruses similar to 4 distinct GII.4 subtypes and 2 patients were linked by the same virus. Of the 14 sites at which there were differences between the consensus sequences of the 2 linked viral genomes, 9 had minor variants present within one or the other patient. Further analysis confirmed that minor variants at all 9 sites in patient B w ere present as the consensus sequence in patient A. CONCLUSIONS: Phylogenetic analysis excluded a common source of infection in this apparent outbreak. Two of 3 patients on the same ward had closely related viruses, raising the possibility of cross-infection despite protective isolation. Analysis of deep sequencing data enabled us to establish the likely direction of nosocomial transmission.

Molecular fingerprinting of Mycobacterium abscessus strains in a cohort of pediatric cystic fibrosis patients.

Forty-one Mycobacterium abscessus complex isolates from 17 pediatric cystic fibrosis (CF) patients were typed using a novel variable-number tandem repeat (VNTR) scheme and an automated repetitive-PCR (rep-PCR) system. Both VNTR and rep-PCR typing methods differentiate between members of the M. abscessus complex. The isolates from individual patients are indistinguishable, and the data strongly suggest that individual CF patients are persistently infected with one strain and also suggests that different CF patients can harbor the same strain.

Use of UV-C radiation to disinfect non-critical patient care items: a laboratory assessment of the Nanoclave Cabinet.

BACKGROUND: The near-patient environment is often heavily contaminated, yet the decontamination of near-patient surfaces and equipment is often poor. The Nanoclave Cabinet produces large amounts of ultraviolet-C (UV-C) radiation (53 W/m2) and is designed to rapidly disinfect individual items of clinical equipment. Controlled laboratory studies were conducted to assess its ability to eradicate a range of potential pathogens including Clostridium difficile spores and Adenovirus from different types of surface. METHODS: Each test surface was inoculated with known levels of vegetative bacteria (10(6) cfu/cm(2)), C. difficile spores (10(2)-10(6) cfu/cm(2)) or Adenovirus (10(9) viral genomes), placed in the Nanoclave Cabinet and exposed for up to 6 minutes to the UV-C light source. Survival of bacterial contaminants was determined via conventional cultivation techniques. Degradation of viral DNA was determined via PCR. Results were compared to the number of colonies or level of DNA recovered from non-exposed control surfaces. Experiments were repeated to incorporate organic soils and to compare the efficacy of the Nanoclave Cabinet to that of antimicrobial wipes. RESULTS: After exposing 8 common non-critical patient care items to two 30-second UV-C irradiation cycles, bacterial numbers on 40 of 51 target sites were consistently reduced to below detectable levels (≥ 4.7 log10 reduction). Bacterial load was reduced but still persisted on other sites. Objects that proved difficult to disinfect using the Nanoclave Cabinet (e.g. blood pressure cuff) were also difficult to disinfect using antimicrobial wipes. The efficacy of the Nanoclave Cabinet was not affected by the presence of organic soils. Clostridium difficile spores were more resistant to UV-C irradiation than vegetative bacteria. However, two 60-second irradiation cycles were sufficient to reduce the number of surface-associated spores from 10(3) cfu/cm(2) to below detectable levels. A 3 log10 reduction in detectable Adenovirus DNA was achieved within 3 minutes; after 6 minutes, viral DNA was undetectable. CONCLUSION: The results of this study suggest that the Nanoclave Cabinet can provide rapid and effective disinfection of some patient-related equipment. However, laboratory studies do not necessarily replicate 'in-use' conditions and further tests are required to assess the usability, acceptability and relative performance of the Nanoclave Cabinet when used in situ.

Role of immunoglobulin supplementation for secondary immunodeficiency associated with chylothorax after pediatric cardiothoracic surgery.

OBJECTIVE: To evaluate whether intravenous immunoglobulin was linked to a reduction in sepsis in patients with prolonged chylothoraces postpediatric cardiothoracic surgery. DESIGN: Retrospective observational cohort study. SETTING: Tertiary pediatric cardiac surgical center. PATIENTS: Children with chylothoraces postcardiothoracic surgery from 1998 to 2006 divided into two groups: with and without intravenous immunoglobulin supplementation. INTERVENTION: Intravenous immunoglobulin supplementation. MEASUREMENTS AND MAIN RESULTS: Thirty-seven with chylothoraces (median duration 14 days; interquartile range, 10-32 and median maximum chyle drainage 1.9 mL/kg/hr; interquartile range, 1-3) were included, and 16 (43%) received intravenous immunoglobulin. The degree of lymphopenia was worse with longer duration of chylothorax (p = .005). There was a trend toward immunoglobulin depletion-IgG (p = .07) and IgM (p = .07) with higher volume chyle loss. Twenty-two of 37 (59%) developed bloodstream infection and 24 of 37 (65%) developed sepsis related to other organ systems. The rate of bloodstream infection and of sepsis in other organ systems was high at 25 (95% confidence interval 17-39) and 23 (95% confidence interval 15-34) episodes per 1,000 intensive care unit days, respectively. Intravenous immunoglobulin was not related to the bloodstream infection rate: adjusted hazard ratio 0.88 (95% confidence interval 0.20-3.94; p = .87) or rate of sepsis in other organ systems: hazard ratio 2.31 (95% confidence interval 0.21-24.29; p = .49) or the proportion surviving to hospital discharge (p = .37). CONCLUSION: Patients with prolonged, large-volume chyle loss had greater secondary immunodeficiency. Although the sample size was small and therefore able to detect only a large treatment effect from intravenous immunoglobulin, infectious outcomes were equal between the two groups.

Antibiotic-impregnated ventriculoperitoneal shunts--a multi-centre British paediatric neurosurgery group (BPNG) study using historical controls.

BACKGROUND: Ventriculoperitoneal shunt infection remains a significant problem. The introduction of antibiotic-impregnated shunt (AIS) systems in the prevention of shunt infection may represent a potential advance; however, there are no randomized controlled trials to establish a robust evidence-based practice. Previously published single-institution cohort studies have provided varying results on the efficacy of AIS systems in the prevention of shunt infection. In this study, we evaluate combined outcomes from three paediatric neurosurgical units in the use of AIS systems for paediatric patients with hydrocephalus. METHODS: The three units established independent databases with data collected from varying time frames. All procedures, where a complete AIS system or part was implanted into patients from 0-16 years in age, were included. The primary outcome measure was shunt infection rate. Shunt procedures were classified as de novo (DNS) and clean revision (CRS). An infant (<1 year) de novo insertion subgroup was also analyzed. AIS shunts were compared to a historical control of non-AIS shunts and results were analysed by centre using an odds ratio with a 95% confidence interval and combined across centres by meta-analysis. RESULTS: A total of 581 AIS implantation procedures were performed in all three units. The comparative non-AIS historical cohort comprised of 1,963 procedures. The pooled effect estimate indicated a clinical advantage for AIS shunts compared to non-AIS shunts, odds ratio (OR), 0.60 (95% CI 0.38, 0.93). The de novo infant group comprised 153 AIS systems, and 465 de novo shunts in the historical non-AIS cohort. Again the pooled effect estimate indicated a clinical advantage for AIS shunts compared to non-AIS shunts, OR 0.38 (95% CI, 0.17; 0.85); however, there was a large overlap of confidence intervals in the results from the different sites indicating the uncertainty in the treatment effect estimates. Over 80% of organisms were gram positive in the infected AIS cohort with a median time to infection of 19 days. Two rifampicin-resistant organisms and three MRSA organisms were detected. CONCLUSION: Data from this exclusively paediatric multi-centre historical control study suggest that AIS may significantly reduce infection rates in de novo and clean revision shunt implants. Although the possibility of bias cannot be excluded due to study design, this is the largest study on an exclusively paediatric cohort comparing standard shunts to AIS implants. Future double-blinded RCTs are needed to confirm AIS efficacy.

Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit.

A recent surge in human mastadenovirus (HAdV) cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate. We compared sequences from 37 patients collected over a 20-month period with sequences from GenBank and our own database of HAdVs. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships, paired with the epidemiological data from routine infection prevention and control (IPC) records and hospital activity data. During this time period, two formal outbreaks had been declared by IPC, while WGS detected nine monophyletic clusters, seven were corroborated by epidemiological evidence and by comparison of single-nucleotide polymorphisms. One of the formal outbreaks was confirmed, and the other was not. Of the five HAdV-associated deaths, three were unlinked and the remaining two considered the source of transmission. Mixed infection was frequent (10%), providing a sentinel source of recombination and superinfection. Immunosuppressed patients harboring a high rate of HAdV positivity require comprehensive surveillance. As a consequence of these findings, HAdV WGS is being incorporated routinely into clinical practice to influence IPC policy contemporaneously.

Brain abscess in children, a two-centre audit: outcomes and controversies.

OBJECTIVE: The aim of this study was to better characterise clinical presentation, management and outcome in infants and children with brain abscess. METHODS: The authors conducted a retrospective, multicentre study in two national reference centres over a 25-year period (1992-2017). During this period, 116 children and 28 infants (age <1 year) with brain abscess were treated. RESULTS: The median age at diagnosis was 101.5 (range: 13-213) months in children and 1 (0-11) month in infants. Significant differences were observed between children and infants. The most common predisposing factor was meningitis in infants (64% of cases vs 3% in children), while it was otolaryngology-related infection in children (31% of cases vs 3.6% in infants). Infants presented more frequently with fever and meningism compared with children. 115 patients were treated with aspiration and 11 with excision. Reoperation was required in 29 children vs 1 infant. The overall mortality rate was 4% (3.4% for children, 7.1% for infants). At 3-month follow-up, the outcome was favourable in 86% of children vs in 68% of infants. CONCLUSION: There is a clear difference between children and infants with brain abscess in terms of predisposing factors, causative organisms and outcome. Despite surgical drainage and directed antibiotic therapy, 25% of patients with brain abscess require reoperation. Mortality is improved compared with historical series; however, long-term morbidity is significant particularly in the infant population.

Silver-impregnated, antibiotic-impregnated or non-impregnated ventriculoperitoneal shunts to prevent shunt infection: the BASICS three-arm RCT.

BACKGROUND: Insertion of a ventriculoperitoneal shunt to treat hydrocephalus is one of the most common neurosurgical procedures worldwide. Shunt infection affects up to 15% of patients, resulting in long hospital stays, multiple surgeries and reduced cognition and quality of life. OBJECTIVES: The aim of this trial was to determine whether or not antibiotic-impregnated ventriculoperitoneal shunts (hereafter referred to as antibiotic shunts) (e.g. impregnated with rifampicin and clindamycin) or silver-impregnated ventriculoperitoneal shunts (hereafter referred to as silver shunts) reduce infection compared with standard ventriculoperitoneal shunts (hereafter referred to as standard shunts). DESIGN: This was a three-arm, superiority, multicentre, parallel-group randomised controlled trial. Patients and a central primary outcome review panel, but not surgeons or operating staff, were blinded to the type of ventriculoperitoneal shunt inserted. SETTING: The trial was set in 21 neurosurgical wards across the UK and the Republic of Ireland. PARTICIPANTS: Participants were patients with hydrocephalus of any aetiology who were undergoing insertion of their first ventriculoperitoneal shunt. INTERVENTIONS: Participants were allocated 1 : 1 : 1 by pressure-sealed envelope to receive a standard non-impregnated, silver-impregnated or antibiotic-impregnated ventriculoperitoneal shunt at the time of insertion. Ventriculoperitoneal shunts are medical devices, and were used in accordance with the manufacturer's instructions for their intended purpose. MAIN OUTCOME MEASURES: The primary outcome was time to ventriculoperitoneal shunt failure due to infection. Secondary outcomes were time to failure for any cause, reason for failure (infection, mechanical), types of ventriculoperitoneal shunt infection, rate of infection after first clean (non-infected) revision and health economics. Outcomes were analysed by intention to treat. RESULTS: Between 26 June 2013 and 9 October 2017, 1605 patients from neonate to 91 years of age were randomised to the trial: n = 36 to the standard shunt, n = 538 to the antibiotic shunt and n = 531 to the silver shunt. Patients who did not receive a ventriculoperitoneal shunt (n = 4) or who had an infection at the time of insertion (n = 7) were not assessed for the primary outcome. Infection occurred in 6.0% (n = 32/533) of those who received the standard shunt, in 2.2% (n = 12/535) of those who received the antibiotic shunt and in 5.9% (n = 31/526) of those who received the silver shunt. Compared with the standard shunt, antibiotic shunts were associated with a lower rate of infection (cause-specific hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80) and a decreased probability of infection (subdistribution hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80). Silver shunts were not associated with a lower rate of infection than standard shunts (cause-specific hazard ratio 0.99, 97.5% confidence interval 0.56 to 1.74). The ventriculoperitoneal shunt failure rate attributable to any cause was 25.0% overall and did not differ between arms. Antibiotic shunts save £135,753 per infection avoided. There were no serious adverse events. LIMITATIONS: It was not possible to blind treating neurosurgeons to the ventriculoperitoneal shunt type. The return rate for patient-reported outcomes was low. Limitations to the economic evaluation included failure to obtain Hospital Episode Statistics data from NHS Digital, as per protocol. Reliance on patient-level information and costing systems data mitigated these limitations. CONCLUSIONS: Antibiotic shunts have a reduced infection rate compared with standard shunts, whereas silver shunts do not. Antibiotic shunts are cost-saving. FUTURE WORK: A sample collection has been established that will enable the study of surrogate markers of ventriculoperitoneal shunt infection in cerebrospinal fluid or blood using molecular techniques. A post hoc analysis to study factors related to shunt failure will be performed as part of a future study. An impact analysis to assess change in practice is planned. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49474281. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 17. See the NIHR Journals Library website for further project information.

Hydrocephalus (commonly known as 'water on the brain') is a condition that can affect all age groups, from babies to the elderly. In hydrocephalus, there is an accumulation of the normal brain fluid in the fluid cavities (ventricles) of the brain. Untreated, hydrocephalus can be life-threatening. The most common treatment involves an operation to insert a tube into the swollen ventricles to drain off the excess fluid. This is called a ventriculoperitoneal shunt. In the UK, 3000­3500 shunt operations are performed each year. The main risks of a shunt operation are infection (surgical meningitis) and blockage without infection. Infection results in the need for at least two further surgeries, antibiotic treatment and a prolonged hospital stay (minimum of 2 weeks). Shunt infections can affect mental abilities and can be life-threatening. People who have blockages without infection, on the other hand, usually need only a single operation to replace the blocked part and only a few days in hospital. Two new types of shunt catheter have been introduced to try to reduce shunt infection: antibiotic-impregnated shunts and silver-impregnated shunts. This study was designed to assess whether or not either of these new shunts reduce infection compared with standard shunts. This study also included an analysis of the cost and health benefits of the different shunts used. A total of 1605 children and adults, who were treated in neurosurgical units across the UK and the Republic of Ireland, participated in this study. Consent was provided by all participants in the trial. Each participant had an equal chance of receiving one of the three shunt types. Shunt infection occurred in 6% of participants receiving standard shunts, 5.9% of participants receiving silver-impregnated shunts and 2.2% of participants receiving antibiotic-impregnated shunts. This study has demonstrated a major reduction in shunt infections in new shunts when using antibiotic-impregnated shunts compared with standard or silver-impregnated shunts. A health economic analysis has indicated that antibiotic-impregnated shunts are cost-saving.

The likelihood of an indeterminate test result from a whole-blood interferon-gamma release assay for the diagnosis of Mycobacterium tuberculosis infection in children correlates with age and immune status.

BACKGROUND: Interferon-gamma release assays for the diagnosis of infection with Mycobacterium tuberculosis have been increasingly used in recent years and are endorsed by national guidelines, but experience regarding their use in children is still limited. METHODS: We retrospectively evaluated the routine use of the QuantiFERON-TB Gold In-Tube assay (QFT-IT) in a pediatric tertiary care center with a high prevalence of immunocompromising conditions. The relationship between age, immune status, and likelihood of an indeterminate test result was analyzed using logistic regression analysis and fractional polynomials. RESULTS: Two hundred thirty-seven tests from 237 children were included in the analysis. Fifty-nine children (25%) were immunocompromised by our definition. An indeterminate test result was obtained in 83 children (35%). The likelihood of an indeterminate test result was inversely correlated with age (P < 0.001) for children who were not known to be immunocompromised, and decreased by 13% per year of age. Impaired immunity (P < 0.001) was independently associated with a higher probability of an indeterminate QFT-IT. Among 161 children with a documented tuberculin skin test, 89% had a concordant QFT-IT (kappa = 0.71). Twelve of 16 patients with culture-proven TB had a positive QFT-IT. CONCLUSION: These data suggest that QFT-IT may not provide a determinate test result in a substantial proportion of children in a tertiary care setting due to the combination of young age and primary and acquired immune deficiencies.

Controlling Legionella pneumophila in water systems at reduced hot water temperatures with copper and silver ionization.

BACKGROUND: Hospital-acquired Legionnaires' disease is associated with the presence of Legionella pneumophila in hospital water systems. In the United Kingdom, the Department of Health recommends maintaining hot water temperatures >55°C and cold water temperatures <20°C at the point of delivery to prevent proliferation of L pneumophila in water systems. In this study, we evaluated the efficacy of copper and silver ionization to control L pneumophila at deliberately reduced hot water temperatures (43°C) within a newly installed water system in a new building linked to a large health care facility in the United Kingdom. METHODS: One thousand, five hundred ninety-eight water samples were collected between September 2011 and June 2017. Samples were tested using accredited methods for L pneumophila, copper and silver ion levels, and total viable counts. Energy consumption and water usage data were also collected to permit carbon emission calculations. RESULTS: The results of 1,598 routine samples from September 2011 to June 2017, and the recordings of temperatures at outlets in this facility, demonstrated effective (100%) L pneumophila control throughout the study period with an average hot water temperature of 42°C. The energy savings and reduction of carbon emissions were calculated to amount to 33% and 24%, respectively, compared to an equivalent temperature-controlled system. Water system management interventions were required to achieve consistently adequate levels of copper and silver across outlets. CONCLUSIONS: This study demonstrated that it is possible to control L pneumophila independent of temperature when copper and silver ionization is introduced into a new building in conjunction with an appropriately managed water system.

Duplex real-time PCR assay for detection of Streptococcus pneumoniae in clinical samples and determination of penicillin susceptibility.

We have developed a duplex real-time PCR for the rapid diagnosis of Streptococcus pneumoniae infection from culture-negative clinical samples with the simultaneous determination of penicillin susceptibility. The assay amplifies a lytA gene target and a penicillin binding protein 2b (pbp2b) gene target in penicillin-susceptible organisms. The assay was shown to be sensitive (detects 0.5 CFU per PCR) and specific for the detection of S. pneumoniae DNA. The assay was validated by comparing pbp2b PCR results with MIC data for 27 S. pneumoniae isolates. All 5 isolates with penicillin MICs of > 1.0 mg/liter were pbp2b real-time PCR negative, as were 9 of the 10 isolates with penicillin MICs of 0.12 to 1.0 mg/liter. One isolate with a penicillin MIC of 0.12 to 1.0 mg/liter gave an equivocal pbp2b real-time PCR result. Twelve isolates were penicillin susceptible (MICs of < or = 0.06 mg/liter) and pbp2b real-time PCR positive. These data were used to establish an algorithm for the interpretation of penicillin susceptibility from the duplex PCR result. pbp2b real-time PCR results were also compared to an established PCR-restriction fragment length polymorphism (RFLP) method previously applied to these 27 isolates and 46 culture-negative clinical samples (containing S. pneumoniae DNA by broad-range 16S rRNA gene PCR). Discordant results were seen for four isolates and six culture-negative clinical samples, as PCR-RFLP could not reliably detect penicillin MICs of 0.12 to 1.0 mg/liter. We report prospective application of the duplex PCR assay to the diagnosis of S. pneumoniae infection from 200 culture-negative clinical specimens sent to the laboratory for diagnostic broad-range 16S rRNA gene PCR. One hundred six were negative in the duplex PCR. Ninety-four were lytA PCR positive, and 70 of these were also pbp2b PCR positive and interpreted as penicillin susceptible. Fourteen were pbp2b PCR negative and interpreted as having reduced susceptibility to penicillin. For the remaining 10 samples, susceptibility to penicillin was not determined.

Shunt infection: is there a near-miss scenario?

OBJECT: The aim of this study was to establish whether microbiological contamination at the time of shunt insertion can be detected and used to predict the likelihood of subsequent shunt infection. METHODS: A prospective study of pediatric patients undergoing primary shunt insertion was undertaken. Following the protocol devised for this study, three swab samples were collected from the surgical wounds during each procedure. These samples were incubated and subcultured, and the isolates were identified and stored. In patients who subsequently presented with clinical evidence of shunt infection, cerebrospinal fluid (CSF) was analyzed using microscopy, tissue cultures, and sensitivity testing. The organisms isolated at the time of shunt insertion and those responsible for subsequent shunt infection were then compared. The study population consisted of 107 pediatric patients. Because one patient underwent placement of an additional contralateral shunt system, there were 108 total shunt insertions yielding 325 swab samples. Organisms were identified in cultures of 50 swab samples (15%) obtained in 40 patients (37%). In seven of these 40 patients (17.5%) a CSF infection subsequently developed. In only one patient was the infectious organism the same as that isolated from the swab specimens. In an additional six patients (8.8%) a CSF infection occurred despite the lack of growth in the cultures from intraoperative swab samples. CONCLUSIONS: The organisms responsible for shunt infection were rarely detected in the operative wound at the time of shunt insertion, leading the authors to conclude that the vulnerable period for bacterial colonization of shunts may not be restricted to the operative procedure as is commonly believed, but may extend throughout the postoperative period of wound healing. These findings have implications not only for a better understanding of the cause of shunt infections but also for the development of strategies to prevent them.

Healthcare-associated infection in pediatric patients on extracorporeal life support: The role of multidisciplinary surveillance.

OBJECTIVE: To describe the use of a multidisciplinary approach to sepsis surveillance and evaluate impact on outcome. DESIGN: Prospective clinical study or clinical audit cycle. SETTING: Tertiary pediatric extracorporeal membrane oxygenation (ECMO) center. PATIENTS: Patients were 215 children supported with ECMO January 1999 to December 2004. INTERVENTIONS: A multidisciplinary team met monthly to evaluate cases of bloodstream infection and mediastinitis, review trends, and update unit policies. Changes in practice were made at the end of 2001 in order to address a perceived high rate of sepsis: a) reeducation; b) introduction of electively preprimed ECMO circuits; and c) preference for neck rather than chest cannulation in cardiac patients. Prophylactic antibiotics were used from preprocedure for 24 hrs only throughout the study. MEASUREMENTS AND MAIN RESULTS: Over the entire study period, 39 children had 47 septic episodes, with a rate of 24.9 per 1000 ECMO days. Multiple logistic regression analyses indicated that infection was associated with duration of ECMO support (odds ratio 1.24; 95% confidence interval 1.15, 1.35 per day) and case type: Closed vs. open chest was protective in cardiac patients (odds ratio 0.08; 95% confidence interval 0.01, 0.50). Infection increased the odds of death by 2.01 (95% confidence interval 1.00, 4.05), but this effect was less important than case type and ECMO days. After policy changes were implemented, there was a reduction in sepsis from 29.3 to 20.1 episodes per 1000 ECMO days. There was reduced sepsis in respiratory patients: neonates from 28.0 to 6.6 and pediatric patients from 42.4 to 16.9 episodes per 1000 ECMO days. Despite policy changes, sepsis remained a problem in cardiac patients with open sternum: 65.1 per 1000 ECMO days. CONCLUSIONS: ECMO support is a high-risk setup for nosocomial infection, in particular for cardiac patients with open sternum for whom antibiotic prophylaxis is justified. Multidisciplinary surveillance offers an excellent approach for quality improvement in this challenging field.

Biochemical and microbial contamination of surgical devices: a quantitative analysis.

Reusable devices are required to be safety processed prior to patient use, including cleaning and disinfection and sterilization. In developing and testing cleaning processes, it is important to understand the levels of soils typically present on devices after surgical use. Previous soil investigations have focused on microbial contamination levels; less is known about biochemical contamination. In this study, microbial and biochemical contamination on a range of surgical instrumentation after patient use were investigated. Analysis included bacteria levels, total organic carbon, protein, and hemoglobin. The highest levels of soil contamination were caused by protein, in contrast with bacteria levels being a minor component of instrument soiling. This study provides a better understanding of the microbial and biochemical levels of soils that are typically present in used surgical devices. These levels can be used to develop artificial test soils for testing cleaning efficacy under laboratory conditions and to further evaluate patient risks from inadequate cleaning.